Role of DNA methylation in perinatal nicotine-induced development of heart ischemia-sensitive phenotype in rat offspring

Oncotarget
Jun KeDaliao Xiao

Abstract

Maternal cigarette smoking increases the risk of cardiovascular disease in offspring. Recently, we have demonstrated that perinatal nicotine exposure alters heart development and increases heart susceptibility to ischemia/reperfusion (I/R) injury in rat offspring. The present study tested the hypothesis that DNA methylation plays a key role in the nicotine-induced development of heart ischemia-sensitive phenotype in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from gestational day 4 until postnatal day 10. After birth, the postnatal offspring were treated with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-Aza) or saline from postnatal day 3 to day 10. Experiments were conducted in 1 month old offspring. Perinatal nicotine increased I/R-induced left ventricular (LV) injury, and decreased post-ischemic recovery of the LV function and coronary flow rate in both male and female offspring. Nicotine differentially increased DNMT3a expression and global DNA methylation levels in LV tissues. Treatment with 5-Aza inhibited nicotine-induced an increase in DNMT3a and global DNA methylation, and blocked the nicotine-induced increase in I/R injury and dysfunction in the heart. In additi...Continue Reading

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Citations

Feb 26, 2019·Clinical Science·Jinhua Tang, Shougang Zhuang
Aug 17, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Tsai-Der ChuangVirender K Rehan
Sep 26, 2019·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Yong LiDaliao Xiao
Jun 26, 2020·Cell Death & Disease·Weifeng YaoZiqing Hei
Mar 10, 2020·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Kun LiuGuang Han
Feb 9, 2021·Frontiers in Pharmacology·Qingxiao HongHuifen Liu
Jun 29, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Keyan WangXiaolong Wang

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Methods Mentioned

BETA
ELISA
protein assay
electrophoresis

Software Mentioned

ImageJ
Kodak ID

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